Crystal Arthropathies

Question 1

What is the epidemiology of gout?

Answer 1

Affects 1% of the population and is more common in men (there uric acid levels rise after puberty)

Question 2

What is ‘gout’?

Answer 2

Where monosodium rate crystals precipitate in the soft tissues and lead to joint destruction and renal damage if not treated

Question 3

What are the main risk factors for the development of gout?

Answer 3

Elevated dietary intake of purines and under excretion of uric acid (renal insufficiency, dehydration and diuretics)

Question 4

How long does it take for elevated uric acid levels to cause an attack of gout?

Answer 4

Approximately 20 years.

Question 5

What is the main cause of gout?

Answer 5

Under excretion of uric acid by the kidneys

Question 6

What is the clinical presentation of gout?

Answer 6

Acute and mono-articular affecting small joints of the lower extremity and usually affects the 1st metatarsal joint, inflammation at this joint is known as podagral. Joint will be red, hot, very tender and pain will start acutely and usually at night.

Question 7

What is podagral?

Answer 7

Inflammation at the 1st metatarsal joint

Question 8

How may gout be diagnosed from synovial fluid?

Answer 8

It will have inflammatory markers (CRP etc) with a WBC greater than 2000/µL with presence of many polymorphonuclear neutrophils.You may also be able to see needle-like urate crystals with polarising light

Question 9

How may gout be diagnosed by imaging (x-ray/ultrasound)?

Answer 9

♣ Soft tissue swelling and increased blood flow
♣ Maintenance of joint space
♣ Erosion OUTSIDE of joint capsule
♣ Erosions have overhanging edges which appear like a rat bite

Question 10

Outline the prognosis of untreated gout

Answer 10

if untreated the attacks will become polyarticular with more proximal and upper extremity joints involved. The attacks will become more frequent and last longer

Question 11

What are tophi?

Answer 11

Urate crystals in soft tissues that develop in half of all patients with untreated gout after 10 years

Question 12

What are the consequences of tophi?

Answer 12

They can lead to bone erosions; the crystals cause a reaction in the granulomatous tissue leading to the production of pro-inflammatory cytokines (IL-1, TNF and IL-6) which leads to the stimulation of osteoclasts due to RANKL expression

Question 13

What is the pathophysiology of gout?

Answer 13

A gout attack is triggered by uncoated monosodium urate crystals or a large sudden change in the concentration of uric acid. Crystals activate IL-1 receptors directly and neutrophils present are phagocytic and will ingest the crystals leading to an inflammatory response

Question 14

How do tophi appear histologically?

Answer 14

Appears as a foreign body-type giant cell reaction to the deposited crystals

Question 15

How may acute gout be treated?

Answer 15

NSAIDs, colchicine (anti-mitotic), corticosteroids, IL-1 biologicals (rilonacept, canakinumab and anakinra), reduced purine intake

Question 16

Name some examples of IL-1 antagonists.

Answer 16

Rilonacept, canakinumab and anakinra

Question 17

How may allopurinol be used in the treatment of gout?

Answer 17

Blocks the action of xanthine oxidase which reduces the genreation of uric acid

Question 18

How may probenecid be used in the treatment of gout?

Answer 18

Increases uric acid excretion

Question 19

How may rasburicase be used in the treatment of gout?

Answer 19

Catalyses the conversion of uric acid to allantoin

Question 20

How can dietary changes be used to treat gout?

Answer 20

Reduce purine intake by eating less yeast, meat extracts, mussels, nuts, mackerel/sardines, avacodos

Question 21

Briefly outline the process of purine metabolism (relevant to gout)

Answer 21

Purines –> converted to xanthine –> xanthine oxidase catalyses conversion to –> urate –> urate oxidase can convert this to allantoin

Question 22

What is pseudogout?

Answer 22

A form of chonedrocalcinosis where there acute deposition of calcium pyrophosphate crystals in and around the joints

Question 23

Outline the pathophysiology of pseudgout

Answer 23

There is release of the calcium pyrophosphate crystals into the joint space, this is followed by phagocytosis of the crystals by monocyte-macrophages or neutrophils – which then release cytokines and cause inflammation. Acute attacks can be triggered by trauma or a rapid reduction of serum calcium concentration.

Question 24

Outline the epidemiology of pseudogout

Answer 24

Around 50% of people aged 85+ have evidence of chrondrocalcinosis

Question 25

Outline how pseudogout may be diagnosed

Answer 25

The crystals are rhomboid shaped and are found in the synovial fluid. These are taken up by neutrophils which try and digest the crystals. Ultrasounds may show calcification within the soft tissue and articular cartilage.

Question 26

How may psuedogout be treated?

Answer 26

Intra-articular corticosteroids and NSAIDs

Question 27

How can you distinguish between gout and pseudogout?

Answer 27

Psuedogout: usually affects the elderly, serum urate levels are normal, involvement of MTP is rare and crystals are rhomboid shaped

Gout: usually affects men and post-menopausal women, serum rate is elevated with rate-bite erosions on x-ray, needle-shaped crystals and involvement of 1st MTP is common

Question 28

What foods are rich in purines?

Answer 28

Beef, pork, lamb, seafood, beer and alcohol

Question 29

Which joint is almost always affected in gout?

Answer 29

1st metatarsal joint

Question 30

How may colchicine be used in the treatment of acute gout?

Answer 30

This is an anti-mitotic which prevents the proliferation of immune cells